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Open data
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Basic information
Entry | Database: PDB / ID: 2no3 | ||||||
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Title | Novel 4-anilinopyrimidines as potent JNK1 Inhibitors | ||||||
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Function / homology | ![]() positive regulation of cell killing / JUN phosphorylation / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | Abad-Zapatero, C. | ||||||
![]() | ![]() Title: Discovery of a new class of 4-anilinopyrimidines as potent c-Jun N-terminal kinase inhibitors: Synthesis and SAR studies. Authors: Liu, M. / Wang, S. / Clampit, J.E. / Gum, R.J. / Haasch, D.L. / Rondinone, C.M. / Trevillyan, J.M. / Abad-Zapatero, C. / Fry, E.H. / Sham, H.L. / Liu, G. #1: ![]() Title: Synthesis and SAR of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as novel, selective c-Jun N-terminal kinase inhibitors. Authors: Liu, M. / Xin, Z. / Clampit, J.E. / Wang, S. / Gum, R.J. / Haasch, D.L. / Trevillyan, J.M. / Abad-Zapatero, C. / Fry, E.H. / Sham, H.L. #2: ![]() Title: Selective aminopyridine-based C-Jun N-terminal kinase inhibitors with cellular activiy Authors: Szczepankiewicz, B.G. / Kosogof, C. / Nelson, L.T.J. / Liu, G. / Zhao, H. / Serby, M.D. / Xin, Z. / Liu, B. / Gum, R.J. / Haasch, D. #3: ![]() Title: Discovery of Potent, Highly Selective and orally bioavailable Pyridine Carboxamide C-jun NH2-terminal kinase inhibitors Authors: Zhao, H. / Serby, M.D. / Xin, Z. / Szczepankiewicz, B.G. / Liu, M. / Kosogof, C. / Liu, B. / Gum, R.J. / Clampit, J.E. / Haasch, D.L. | ||||||
History |
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Remark 999 | SEQUENCE THE NATIVE, UNMUTATED SEQUENCE IS THE SAME AS THE P45983-2 ISOFORM. THE INTRODUCED ...SEQUENCE THE NATIVE, UNMUTATED SEQUENCE IS THE SAME AS THE P45983-2 ISOFORM. THE INTRODUCED MUTATIONS (THR183>GLU, TYR185>GLU) ARE INTENDED TO MIMIC THE ACTIVATED FORM OF THE KINASE UPON PHOSPHORYLATION OF THOSE TWO RESIDUES. |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 160.7 KB | Display | ![]() |
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PDB format | ![]() | 128.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 2h96S S: Starting model for refinement |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 42919.559 Da / Num. of mol.: 2 / Fragment: JNK1 residues 1-364 / Mutation: T183E, Y183E Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() References: UniProt: P45983, ![]() #2: Protein/peptide | Mass: 1345.612 Da / Num. of mol.: 2 / Fragment: PEPJIP1 PEPTIDE / Source method: obtained synthetically / Details: The sequence is found naturally in homo sapiens #3: Chemical | ChemComp-SO4 / ![]() #4: Chemical | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 4.97 Å3/Da / Density % sol: 75.24 % |
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Crystal grow![]() | Temperature: 277 K / Method: vapor diffusion / pH: 6.2 Details: PROTEIN WAS PREINCUBATED WITH THE JIP1 PEPTIDE AT A 5X MOLAR EXCESS. PROTEIN CONCENTRATION 9- 12.6 MG/ML. HANGING DROPS CONSISTED OF 2UL PROTEIN PLUS 2 UL WELL SOLUTION. WELL SOLUTION:2.8-3. ...Details: PROTEIN WAS PREINCUBATED WITH THE JIP1 PEPTIDE AT A 5X MOLAR EXCESS. PROTEIN CONCENTRATION 9- 12.6 MG/ML. HANGING DROPS CONSISTED OF 2UL PROTEIN PLUS 2 UL WELL SOLUTION. WELL SOLUTION:2.8-3.1 M AMMONIUM SULFATE, 10- 14% GLYCEROL. FOR CO-CRYSTALLIZATION EXPERIMENT WITH THE COMPOUND, THE COMPOUND WAS DISSOLVED IN DMSO AT 100 MM CONCENTRATION. ALLOW TO INCUBATE FOR AT LEAST AN HOUR ON ICE. SOLUTION WAS SPUN FOR 5 MINUTES AT 2000G PRIOR TO SETTING UP FOR CRYSTALLIZATION., pH 6.20, VAPOR DIFFUSION, temperature 277.0K |
-Data collection
Diffraction | Mean temperature: 110 K |
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Diffraction source | Source: ![]() |
Detector | Type: MAR CCD 165 mm / Detector: CCD / Date: Jan 6, 2005 / Details: Osmic Mirrors |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength![]() |
Reflection | Resolution: 3.2→20 Å / Num. all: 28588 / Num. obs: 27814 / % possible obs: 94.5 % / Observed criterion σ(I): 1 / Redundancy: 5.6 % / Biso Wilson estimate: 36.8 Å2 / Rmerge(I) obs: 0.083 / Rsym value: 0.083 / Net I/σ(I): 15.3 |
Reflection shell | Resolution: 3.2→3.31 Å / Redundancy: 4.2 % / Rmerge(I) obs: 0.454 / Mean I/σ(I) obs: 1.6 / Num. unique all: 2866 / Rsym value: 0.812 / % possible all: 98.3 |
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Processing
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Refinement | Method to determine structure![]() ![]() Starting model: entry 2h96 Resolution: 3.2→19.98 Å / Rfactor Rfree error: 0.006 / Data cutoff high absF: 162862.68 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 2 / Stereochemistry target values: Engh & Huber
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 24.1807 Å2 / ksol: 0.224291 e/Å3 | |||||||||||||||||||||||||
Displacement parameters | Biso mean: 65.1 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 3.2→19.98 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.2→3.31 Å / Rfactor Rfree error: 0.027 / Total num. of bins used: 10
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Xplor file |
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